Ischemic Cholangiopathy After Controlled Donation After Cardiac Death Liver Transplantation

Jay, Colleen L.; Lyuksemburg, Vadim; Ladner, Daniela P.; Wang, Edward; Caicedo, Juan C.; Holl, Jane L.; Abécassis, Michaël; Skaro, Anton I.

doi:10.1097/sla.0b013e318204e658

Cited by 288 publications

(279 citation statements)

References 21 publications

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“…1 The presented patient's case highlights the potential benefits of NMLP, though these need to be validated by adequately powered clinical trials.…”

Section: Discussionmentioning

confidence: 95%

“…The potential benefit of using these grafts is often offset by post-transplant complications including PNF, delayed graft function, and ischemia-type biliary strictures that are especially seen in recipients of donation after cardiac death (DCD) livers. 1 Therefore, organ discard rates have been increasing, most commonly for degree of graft steatosis, inadequate perfusion, or prolonged warm and/or cold ischemia time. 2 Ischaemia/reperfusion injury is the fundamental cause of graft damage following static cold storage.…”

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confidence: 99%

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First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

et al. 2015

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“…1 The presented patient's case highlights the potential benefits of NMLP, though these need to be validated by adequately powered clinical trials.…”

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

et al. 2015

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“…Similarly, the reported data, limited by size, do not address the issue of ischemic cholangiopathy, a complication strongly associated with DCD liver transplantation (27,28). Experimental data from large animal studies, specifically investigating biliary epithelial recovery following a period of warm ischemic and NMP, suggest that warm oxygen delivery may provide a critical advantage (29,30).…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Ravikumar

Jassem

Mergental

et al. 2016

American Journal of Transplantation

418

412

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Joint first authors. ISRCTN 14355416.The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ) versus , p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.Abbreviations: AST, aspartate transaminase; DBD, donation after brain death; DCD, donation after circulatory death; IRI, ischemia-reperfusion injury; IVC, inferior vena cava; MELD, model for end-stage liver disease; NHSBT, National Health Service Blood and Transplant; NMP, normothermic machine perfusion

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“…The advent of DCD lung donation has resulted in a 28% increase in transplant numbers in Australia with outcomes comparable to those from NDD donors (5). Livers, however, appear more sensitive to the effects of warm ischemia, with increasing rates of ischemic biliary strictures and worse survival following DCD liver transplantation (6,7). Similar concerns regarding the impact of warm ischemia and irreversible ischemic injury have thus far precluded the use of DCD hearts as cardiac allografts.…”

Section: Introductionmentioning

confidence: 98%

Increasing the Tolerance of DCD Hearts to Warm Ischemia by Pharmacological Postconditioning

Iyer

Gao

Doyle

et al. 2014

American Journal of Transplantation

116

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Donation after circulatory death (DCD) offers a potential additional source of cardiac allografts. We used a porcine asphyxia model to evaluate viability of DCD hearts subjected to warm ischemic times (WIT) of 20-40 min prior to flushing with Celsior (C) solution. We then assessed potential benefits of supplementing C with erythropoietin, glyceryl trinitrate and zoniporide (Cs), a combination that we have shown previously to activate ischemic postconditioning pathways. Hearts flushed with C/Cs were assessed for functional, biochemical and metabolic recovery on an ex vivo working heart apparatus. Hearts exposed to 20-min WIT showed full recovery of functional and metabolic profiles compared with control hearts (no WIT). Hearts subjected to 30-or 40-min WIT prior to C solution showed partial and no recovery, respectively. Hearts exposed to 30-min WIT and Cs solution displayed complete recovery, while hearts exposed to 40-min WIT and Cs solution demonstrated partial recovery. We conclude that DCD hearts flushed with C solution demonstrate complete recovery up to 20-min WIT after which there is rapid loss of viability. Cs extends the limit of WIT tolerability to 30 min. DCD hearts with 30-min WIT may be suitable for transplantation and warrant assessment in a transplant model.

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Ischemic Cholangiopathy After Controlled Donation After Cardiac Death Liver Transplantation

Cited by 288 publications

References 21 publications

First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Increasing the Tolerance of DCD Hearts to Warm Ischemia by Pharmacological Postconditioning

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